Subcortical elevation of metabolism in Parkinson's disease--a critical reappraisal in the context of global mean normalization

Per Borghammer; Paul Cumming; Joel Aanerud; Stefan Förster; Albert Gjedde

doi:10.1016/j.neuroimage.2009.05.040

Subcortical elevation of metabolism in Parkinson's disease--a critical reappraisal in the context of global mean normalization

Per Borghammer, Paul Cumming, Joel Aanerud, Stefan Förster, Albert Gjedde

Department of Neuroscience

46 Citations (Scopus)

Abstract

In a recent issue of NeuroImage, we presented evidence that biased global mean (GM) normalization of brain PET data can generate the appearance of subcortical foci with relative hypermetabolism in patients with Parkinson's disease (PD), and other degenerative disorders. In a commentary to our article, Ma and colleagues presented a study seeking to establish that a pattern of widespread hypermetabolism, known as the Parkinson's disease related pattern (PDRP) is a genuine metabolic feature of PD. In the present paper, we respond to the arguments presented by Ma et al., and we provide a critical reappraisal of the evidence for the existence of the PDRP. To this end, we present new analyses of PET data sets, which demonstrate that very similar patterns of relative subcortical increases are seen in PD, Alzheimer's disease, hepatic encephalopathy, healthy aging, and simulation data. Furthermore, longitudinal studies of PD previously reported relative hypermetabolism in very small anatomical structures such as the subthalamic nucleus. We now demonstrate how focal hypermetabolism attributed to small nuclei can similarly arise as a consequence of GM normalization. Finally, we give a comprehensive summary of the entire deoxyglucose autoradiography literature on acquired parkinsonism in experimental animals. Based on this evidence, we conclude that (1) there is no quantitative evidence for widespread subcortical hypermetabolism in PD, (2) very similar patterns of subcortical hyperactivity are evident in various other brain disorders whenever GM normalization is utilized, and (3) the PDRP is not evident in animal models of PD. In the absence of quantitative evidence for the PDRP, our alternative interpretation of normalization bias seems the more parsimonious explanation for the reports of relative hypermetabolism in PD.

Original language	English
Journal	NeuroImage
Volume	47
Issue number	4
Pages (from-to)	1514-21
Number of pages	7
ISSN	1053-8119
DOIs	https://doi.org/10.1016/j.neuroimage.2009.05.040
Publication status	Published - 2009

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10.1016/j.neuroimage.2009.05.040

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@article{88d41ba089cc11df928f000ea68e967b,

title = "Subcortical elevation of metabolism in Parkinson's disease--a critical reappraisal in the context of global mean normalization",

abstract = "In a recent issue of NeuroImage, we presented evidence that biased global mean (GM) normalization of brain PET data can generate the appearance of subcortical foci with relative hypermetabolism in patients with Parkinson's disease (PD), and other degenerative disorders. In a commentary to our article, Ma and colleagues presented a study seeking to establish that a pattern of widespread hypermetabolism, known as the Parkinson's disease related pattern (PDRP) is a genuine metabolic feature of PD. In the present paper, we respond to the arguments presented by Ma et al., and we provide a critical reappraisal of the evidence for the existence of the PDRP. To this end, we present new analyses of PET data sets, which demonstrate that very similar patterns of relative subcortical increases are seen in PD, Alzheimer's disease, hepatic encephalopathy, healthy aging, and simulation data. Furthermore, longitudinal studies of PD previously reported relative hypermetabolism in very small anatomical structures such as the subthalamic nucleus. We now demonstrate how focal hypermetabolism attributed to small nuclei can similarly arise as a consequence of GM normalization. Finally, we give a comprehensive summary of the entire deoxyglucose autoradiography literature on acquired parkinsonism in experimental animals. Based on this evidence, we conclude that (1) there is no quantitative evidence for widespread subcortical hypermetabolism in PD, (2) very similar patterns of subcortical hyperactivity are evident in various other brain disorders whenever GM normalization is utilized, and (3) the PDRP is not evident in animal models of PD. In the absence of quantitative evidence for the PDRP, our alternative interpretation of normalization bias seems the more parsimonious explanation for the reports of relative hypermetabolism in PD.",

author = "Per Borghammer and Paul Cumming and Joel Aanerud and Stefan F{\"o}rster and Albert Gjedde",

note = "Keywords: Brain; Fluorodeoxyglucose F18; Humans; Image Interpretation, Computer-Assisted; Models, Neurological; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Up-Regulation",

year = "2009",

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T1 - Subcortical elevation of metabolism in Parkinson's disease--a critical reappraisal in the context of global mean normalization

AU - Borghammer, Per

AU - Cumming, Paul

AU - Aanerud, Joel

AU - Förster, Stefan

AU - Gjedde, Albert

N1 - Keywords: Brain; Fluorodeoxyglucose F18; Humans; Image Interpretation, Computer-Assisted; Models, Neurological; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Up-Regulation

PY - 2009

Y1 - 2009

N2 - In a recent issue of NeuroImage, we presented evidence that biased global mean (GM) normalization of brain PET data can generate the appearance of subcortical foci with relative hypermetabolism in patients with Parkinson's disease (PD), and other degenerative disorders. In a commentary to our article, Ma and colleagues presented a study seeking to establish that a pattern of widespread hypermetabolism, known as the Parkinson's disease related pattern (PDRP) is a genuine metabolic feature of PD. In the present paper, we respond to the arguments presented by Ma et al., and we provide a critical reappraisal of the evidence for the existence of the PDRP. To this end, we present new analyses of PET data sets, which demonstrate that very similar patterns of relative subcortical increases are seen in PD, Alzheimer's disease, hepatic encephalopathy, healthy aging, and simulation data. Furthermore, longitudinal studies of PD previously reported relative hypermetabolism in very small anatomical structures such as the subthalamic nucleus. We now demonstrate how focal hypermetabolism attributed to small nuclei can similarly arise as a consequence of GM normalization. Finally, we give a comprehensive summary of the entire deoxyglucose autoradiography literature on acquired parkinsonism in experimental animals. Based on this evidence, we conclude that (1) there is no quantitative evidence for widespread subcortical hypermetabolism in PD, (2) very similar patterns of subcortical hyperactivity are evident in various other brain disorders whenever GM normalization is utilized, and (3) the PDRP is not evident in animal models of PD. In the absence of quantitative evidence for the PDRP, our alternative interpretation of normalization bias seems the more parsimonious explanation for the reports of relative hypermetabolism in PD.

AB - In a recent issue of NeuroImage, we presented evidence that biased global mean (GM) normalization of brain PET data can generate the appearance of subcortical foci with relative hypermetabolism in patients with Parkinson's disease (PD), and other degenerative disorders. In a commentary to our article, Ma and colleagues presented a study seeking to establish that a pattern of widespread hypermetabolism, known as the Parkinson's disease related pattern (PDRP) is a genuine metabolic feature of PD. In the present paper, we respond to the arguments presented by Ma et al., and we provide a critical reappraisal of the evidence for the existence of the PDRP. To this end, we present new analyses of PET data sets, which demonstrate that very similar patterns of relative subcortical increases are seen in PD, Alzheimer's disease, hepatic encephalopathy, healthy aging, and simulation data. Furthermore, longitudinal studies of PD previously reported relative hypermetabolism in very small anatomical structures such as the subthalamic nucleus. We now demonstrate how focal hypermetabolism attributed to small nuclei can similarly arise as a consequence of GM normalization. Finally, we give a comprehensive summary of the entire deoxyglucose autoradiography literature on acquired parkinsonism in experimental animals. Based on this evidence, we conclude that (1) there is no quantitative evidence for widespread subcortical hypermetabolism in PD, (2) very similar patterns of subcortical hyperactivity are evident in various other brain disorders whenever GM normalization is utilized, and (3) the PDRP is not evident in animal models of PD. In the absence of quantitative evidence for the PDRP, our alternative interpretation of normalization bias seems the more parsimonious explanation for the reports of relative hypermetabolism in PD.

U2 - 10.1016/j.neuroimage.2009.05.040

DO - 10.1016/j.neuroimage.2009.05.040

M3 - Journal article

C2 - 19465133

SN - 1053-8119

VL - 47

SP - 1514

EP - 1521

JO - NeuroImage

JF - NeuroImage

IS - 4

ER -

Subcortical elevation of metabolism in Parkinson's disease--a critical reappraisal in the context of global mean normalization

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